These studies are designed to assess the capacity of hormonally-active chemicals to alter hepatic metabolism and to determine if changes in the endocrine environment can influence hepatotoxic responses. The rat is used as the experimental model. The initial focus has involved sex-differentiation of the hepatotoxic effects of cadmium; male liver monooxygenases activities are repressed by cadmium whereas female enzymes are unaffected by this treatment. Male sensitivity to cadmium appears to reflect the amount of cadmium sensitive hemoproteins (detected on SDS gels and by hemoprotein synthesis/degradation studies) which are under hypophyseal control.